Slc39a4 in the small intestine predicts zinc absorption and utilization: a comprehensive analysis of zinc transporter expression in response to diets of varied zinc content in young mice

Abstract

Zinc homeostasis is primarily maintained by zinc transporters that regulate zinc uptake and efflux in the small intestine; however, the relative contribution of the many zinc transporters identified (Slc39a1-14, Slc30a1-10) to dietary zinc absorption and utilization remains unknown. The objective of this study was to determine the expression of Slc39a1-14 and Slc30a1-10 in the small intestine and their relative contribution to dietary zinc absorption in mice. Five-week-old male C57BL/6J mice were fed modified AIN-93G diets containing <1, 30, or 100ppm zinc (n=15 mice/diet). Following 1 week of feeding, mice were given an oral gavage containing 67Zn and liver and plasma isotope appearance was determined 6-h later by ICP-MS. Expression of Slc39a1-14 and Slc30a1-10 was determined in mucosa from duodenum, jejunum, and ileum. Plasma and liver total zinc concentrations were not different after one week of feeding (P>.05). Liver and plasma appearance of 67Zn was greater in mice fed <1ppm compared to the 30ppm (P<.0001) and 100ppm (P<.0001) zinc diets. With the exception of Slc39a2, Slc39a12, Slc30a3, and Slc30a8, the remaining zinc transporters were expressed across all diets and intestinal segments. Expression of Slc39a4, Slc39a11, and Slc30a6 changed with diet (Pdiet<.05 for all); expression of Slc39a5, Slc39a7, Slc39a11, Slc39a14, Slc30a1, Slc30a2, Slc30a4, Slc30a5, Slc30a7, and Slc30a10 changed by intestinal segment (Psegment<.05 for all). Slc39a4 was the only transporter positively associated with liver (r2=0.316, P<.001) and plasma (r2=0.189, P<.01) 67Zn appearance. Although most zinc transporters are expressed in the small intestine, intestinal Slc39a4 predicts fractional zinc absorption and utilization in young mice.